Ocurrence enzootic hematuria in buffaloes in Brazil: epidemiological, clinical, and pathological aspects

ABSTRACT: It is reported the occurrence of enzootic hematuria (EH) in buffaloes in Brazil after performing an epidemiological survey and clinicopathological analises. To date, EH caused by ingestion of Pteridium esculentum subsp. arachnoideum, a radiomimetic plant popularly known as bracken fern, has not been described in this species in Brazil. Bovine EH is responsible for high economic losses in Brazils Southeast Region not only because of the deaths it causes, but also owing to its negative effect on productivity. In São José do Barreiro County, São Paulo, some farmers in areas with a high incidence of bovine EH have been replacing cattle with buffaloes, based on the premise that the latter would be more resistant to poisoning by ingestion of Pteridium spp. However, even though initial observations indicated that buffaloes are indeed less sensitive than cattle to the toxic principle of Pteridium spp., cases of hematuria in this species have been reported. According to preliminary date, EH only occurs in buffaloes over six years of age. Macroscopic examination revealed a thickened urinary vesicle mucosa, along with multiple foci of ulcerated, exophytic, verrucous, and pedunculated lesions. In one of the buffaloes studied, the bladder wall was ruptured and exhibited marked secondary inflammation. Histologically, neoplastic and non-neoplastic changes similar to those described in cattle poisoned by Pteridium spp. were observed. The neoplasms found included papilloma, carcinoma in situ, urothelial carcinoma (low and high grade), inverted, microcystic, and trabecular variants, urothelial carcinoma with divergent differentiation (squamous and glandular), squamous cell carcinoma, lymphangioma, hemangioma, and hemangiosarcoma. There was also coexistence of epithelial and mesenchymal neoplasms. Bovine papillomavirus particles were not detected by polymerase chain reaction in the bladder samples analyzed.

RESUMO: Descreve-se, através de levantamento epidemiológico e avaliação clínico-patológica, a ocorrência de hematúria enzoótica (HE) em búfalos no Brasil. Essa condição, causada pela ingestão da planta radiomimética Pteridium esculentum subsp. arachnoideum, conhecida popularmente como samambaia ou samambaia do campo, até então não havia sido descrita nessa espécie no Brasil. Na Região Sudeste, a HE bovina é responsável por elevadas perdas econômicas, devidas não apenas aos óbitos, mas também em função da queda de produtividade. No município de São José do Barreiro/SP, alguns produtores de áreas com alta incidência de HE bovina, vêm substituindo os bovinos por búfalos, com base na premissa de que estes seriam mais resistentes à intoxicação. Embora, de acordo com observações iniciais, os búfalos realmente sejam menos sensíveis que os bovinos ao princípio tóxico de Pteridium spp., ainda assim, tem-se verificado a ocorrência de casos de hematúria nessa espécie. De acordo com o levantamento inicial, a HE só ocorre em búfalos com idade a partir de seis anos. Ao exame macroscópico, verificou-se a mucosa da bexiga espessa, com múltiplos focos de lesões ulceradas, exofíticas, papiliformes, verrucosas, pedunculadas. Histologicamente, foram observadas alterações neoplásicas e não neoplásicas semelhantes às descritas nos bovinos com HE. Entre as neoplasias foram encontrados papiloma, carcinoma in situ, carcinoma urotelial (baixo e alto grau), variantes invertida, microcística e trabecular, carcinoma urotelial com diferenciação divergente (escamosa e glandular), carcinoma de células escamosas, linfangioma, hemangioma e hemangiossarcoma. Ocorreu também coexistência entre neoplasias epiteliais e mesenquimais. Não foram detectadas partículas de papilomavírus bovino pelo teste PCR nas amostras de bexiga analisadas.

Ocurrence enzootic hematuria in buffaloes in Brazil: epidemiological, clinical, and pathological aspects / Ocorrência de hematúria enzoótica em búfalos no Brasil: aspectos epidemiológicos, clínicos e patológicos

It is reported the occurrence of enzootic hematuria (EH) in buffaloes in Brazil after performing an epidemiological survey and clinicopathological analises. To date, EH caused by ingestion of Pteridium esculentum subsp. arachnoideum, a radiomimetic plant popularly known as "bracken fern", has not been described in this species in Brazil. Bovine EH is responsible for high economic losses in Brazil's Southeast Region not only because of the deaths it causes, but also owing to its negative effect on productivity. In São José do Barreiro County, São Paulo, some farmers in areas with a high incidence of bovine EH have been replacing cattle with buffaloes, based on the premise that the latter would be more resistant to poisoning by ingestion of Pteridium spp. However, even though initial observations indicated that buffaloes are indeed less sensitive than cattle to the toxic principle of Pteridium spp., cases of hematuria in this species have been reported. According to preliminary date, EH only occurs in buffaloes over six years of age. Macroscopic examination revealed a thickened urinary vesicle mucosa, along with multiple foci of ulcerated, exophytic, verrucous, and pedunculated lesions. In one of the buffaloes studied, the bladder wall was ruptured and exhibited marked secondary inflammation. Histologically, neoplastic and non-neoplastic changes similar to those described in cattle poisoned by Pteridium spp. were observed. The neoplasms found included papilloma, carcinoma in situ, urothelial carcinoma (low and high grade), inverted, microcystic, and trabecular variants, urothelial carcinoma with divergent differentiation (squamous and glandular), squamous cell carcinoma, lymphangioma, hemangioma, and hemangiosarcoma. There was also coexistence of epithelial and mesenchymal neoplasms. Bovine papillomavirus particles were not detected by polymerase chain reaction in the bladder samples analyzed.

Descreve-se, através de levantamento epidemiológico e avaliação clínico-patológica, a ocorrência de hematúria enzoótica (HE) em búfalos no Brasil. Essa condição, causada pela ingestão da planta radiomimética Pteridium esculentum subsp. arachnoideum, conhecida popularmente como "samambaia" ou "samambaia do campo", até então não havia sido descrita nessa espécie no Brasil. Na Região Sudeste, a HE bovina é responsável por elevadas perdas econômicas, devidas não apenas aos óbitos, mas também em função da queda de produtividade. No município de São José do Barreiro/SP, alguns produtores de áreas com alta incidência de HE bovina, vêm substituindo os bovinos por búfalos, com base na premissa de que estes seriam mais resistentes à intoxicação. Embora, de acordo com observações iniciais, os búfalos realmente sejam menos sensíveis que os bovinos ao princípio tóxico de Pteridium spp., ainda assim, tem-se verificado a ocorrência de casos de hematúria nessa espécie. De acordo com o levantamento inicial, a HE só ocorre em búfalos com idade a partir de seis anos. Ao exame macroscópico, verificou-se a mucosa da bexiga espessa, com múltiplos focos de lesões ulceradas, exofíticas, papiliformes, verrucosas, pedunculadas. Histologicamente, foram observadas alterações neoplásicas e não neoplásicas semelhantes às descritas nos bovinos com HE. Entre as neoplasias foram encontrados papiloma, carcinoma in situ, carcinoma urotelial (baixo e alto grau), variantes invertida, microcística e trabecular, carcinoma urotelial com diferenciação divergente (escamosa e glandular), carcinoma de células escamosas, linfangioma, hemangioma e hemangiossarcoma. Ocorreu também coexistência entre neoplasias epiteliais e mesenquimais. Não foram detectadas partículas de papilomavírus bovino pelo teste PCR nas amostras de bexiga analisadas.

Aß31-35 Decreases Neprilysin-Mediated Alzheimer's Amyloid-ß Peptide Degradation.

Alzheimer's disease is associated with the deposition of extracellular senile plaques, made primarily of amyloid-ß (Aß), particularly peptides Aß1-42 and Aß1-40. Neprilysin, or neutral endopeptidase (NEP), catalyzes proteolysis of the amyloid peptides (Aß) and is recognized as one of the major regulators of the levels of these peptides in the brain, preventing Aß accumulation and plaque formation. Here, we used a combination of techniques to elucidate the mechanism of Aß binding and cleavage by NEP. Our findings indicate that the Aß31-X cleavage products remain bound to the neprilysin active site, reducing proteolytic activity. Interestingly, it was already shown that this Aß31-35 sequence is also critical for recognition of Aß peptides by other targets, such as the serpin-enzyme complex receptor in neuronal cells.

The milk-derived lactoferrin inhibits V-ATPase activity by targeting its V1 domain.

Lactoferrin (Lf), a bioactive milk protein, exhibits strong anticancer and antifungal activities. The search for Lf targets and mechanisms of action is of utmost importance to enhance its effective applications. A common feature among Lf-treated cancer and fungal cells is the inhibition of a proton pump called V-ATPase. Lf-driven V-ATPase inhibition leads to cytosolic acidification, ultimately causing cell death of cancer and fungal cells. Given that a detailed elucidation of how Lf and V-ATPase interact is still missing, herein we aimed to fill this gap by employing a five-stage computational approach. Molecular dynamics simulations of both proteins were performed to obtain a robust sampling of their conformational landscape, followed by clustering, which allowed retrieving representative structures, to then perform protein-protein docking. Subsequently, molecular dynamics simulations of the docked complexes and free binding energy calculations were carried out to evaluate the dynamic binding process and build a final ranking based on the binding affinities. Detailed atomist analysis of the top ranked complexes clearly indicates that Lf binds to the V1 cytosolic domain of V-ATPase. Particularly, our data suggest that Lf binds to the interfaces between A/B subunits, where the ATP hydrolysis occurs, thus inhibiting this process. The free energy decomposition analysis further identified key binding residues that will certainly aid in the rational design of follow-up experimental studies, hence bridging computational and experimental biochemistry.

Poisoning by Megathyrsus maximus (Sin. Panicum maximum) cv. Colonião in horses in the state of Rio de Janeiro

ABSTRACT: Colic outbreaks in horses have been associated with the grazing of several Megathyrsus maximus (Sin. Panicum maximum) cultivars in the North and Central-West regions of Brazil. In this paper, we report a horse colic outbreak in the Southeast region of Brazil caused by ingestion of the Colonião cultivar of M. maximus, which has not previously been considered as toxic. The five affected horses belonged to the Veterinary Platoon based at the Central Ammunition Deposit of the Brazilian Army in the city of Paracambi, Rio de Janeiro state, Brazil. The horses had access to treated water and commercial concentrate, and were located in a field of M. maximus at the time of the outbreak. All horses exhibited clinical signs of colic and bloat, and three of them died. The extend of the clinical course ranged from four to five days in the three animals that died; in the two animals that recovered from the colic episodes, the extend of the clinical courses were 10 and 15 days. Necropsy findings revealed intestinal and gastric bloating and hemorrhages involving the intestinal wall. Light microscopy showed moderate diffuse lymphoplasmacytic and eosinophilic enteritis with multifocal erosions, in addition to submucosal edema associated with multifocal vasculitis. The pathogenesis of colic caused by M. maximus ingestion in horses has not yet been elucidated. Some authors have suggested that higher starch concentrations in M. maximus during the rainy season may be responsible for the toxicity of this plant. However, the findings of this study do not support this hypothesis. As a prophylactic measure, it is suggested that horses do not graze exclusively M. maximus at the beginning of rainy periods, in which regrowth of this grass occurs. In Brazil, outbreaks of horse colic associated with ingestion of varieties of Megathyrsus can also occur outside the North and Midwest regions, under specific climate conditions.

RESUMO: Surtos de cólica em equinos vêm sendo associados ao pastejo de várias cultivares de Megathyrsus maximus (Sin. Panicum maximum) nas regiões Norte e Centro-Oeste do Brasil. Neste trabalho relata-se um surto de cólica em equinos determinado pela ingestão da variedade Colonião de M. maximus, cultivar até então não descrita como tóxico. Os cinco equinos, oriundos do Pelotão de Veterinária do Centro de munição do Exército situado no município de Paracambi/RJ, estavam em uma mesma pastagem de M. maximus, tinham acesso à água tratada e ao concentrado comercial para equinos. Todos os equinos tiveram sinais clínicos de cólica por timpanismo e três deles morreram. O curso clínico variou de quatro a cinco dias nos três equinos que morreram e de 10 a 15 dias nos dois equinos que recuperaram-se da cólica. À necropsia, os principais achados foram timpanismo intestinal e gástrico e hemorragias na parede intestinal. À microscopia havia enterite linfoplasmocítica e eosinofílica difusa moderada com erosões multifocais e edema submucoso associado à vasculite multifocal. A patogênese da cólica pela ingestão de M. maximus ainda não foi elucidada, no entanto, alguns autores têm sugerido que uma maior concentração de amido presente na forrageira durante o período de chuvas possa ser responsável pela ação tóxica da planta. Contudo as observações aqui levantadas não dão suporte a essa hipótese. Sugere-se como medida profilática evitar o pastejo exclusivo de M. maximus por cavalos, por meio de pastagens alternativas, principalmente durante o início das chuvas e rebrota da pastagem. Demonstra-se que, no Brasil, os surtos de cólica em equinos associados à ingestão de variedades de Megathyrsus, também podem ocorrer fora das regiões Norte e Centro-Oeste, desde que existam condições climáticas especiais.

Poisoning by Megathyrsus maximus (Sin. Panicum maximum) cv. Colonião in horses in the state of Rio de Janeiro / Intoxicação por Megathyrsus maximus (Sin. Panicum maximum) cv. Colonião em equinos no estado do Rio de Janeiro

Colic outbreaks in horses have been associated with the grazing of several Megathyrsus maximus (Sin. Panicum maximum) cultivars in the North and Central-West regions of Brazil. In this paper, we report a horse colic outbreak in the Southeast region of Brazil caused by ingestion of the "Colonião" cultivar of M. maximus, which has not previously been considered as toxic. The five affected horses belonged to the Veterinary Platoon based at the Central Ammunition Deposit of the Brazilian Army in the city of Paracambi, Rio de Janeiro state, Brazil. The horses had access to treated water and commercial concentrate, and were located in a field of M. maximus at the time of the outbreak. All horses exhibited clinical signs of colic and bloat, and three of them died. The extend of the clinical course ranged from four to five days in the three animals that died; in the two animals that recovered from the colic episodes, the extend of the clinical courses were 10 and 15 days. Necropsy findings revealed intestinal and gastric bloating and hemorrhages involving the intestinal wall. Light microscopy showed moderate diffuse lymphoplasmacytic and eosinophilic enteritis with multifocal erosions, in addition to submucosal edema associated with multifocal vasculitis. The pathogenesis of colic caused by M. maximus ingestion in horses has not yet been elucidated. Some authors have suggested that higher starch concentrations in M. maximus during the rainy season may be responsible for the toxicity of this plant. However, the findings of this study do not support this hypothesis. As a prophylactic measure, it is suggested that horses do not graze exclusively M. maximus at the beginning of rainy periods, in which regrowth of this grass occurs. In Brazil, outbreaks of horse colic associated with ingestion of varieties of Megathyrsus can also occur outside the North and Midwest regions, under specific climate conditions.(AU)

Surtos de cólica em equinos vêm sendo associados ao pastejo de várias cultivares de Megathyrsus maximus (Sin. Panicum maximum) nas regiões Norte e Centro-Oeste do Brasil. Neste trabalho relata-se um surto de cólica em equinos determinado pela ingestão da variedade Colonião de M. maximus, cultivar até então não descrita como tóxico. Os cinco equinos, oriundos do Pelotão de Veterinária do Centro de munição do Exército situado no município de Paracambi/RJ, estavam em uma mesma pastagem de M. maximus, tinham acesso à água tratada e ao concentrado comercial para equinos. Todos os equinos tiveram sinais clínicos de cólica por timpanismo e três deles morreram. O curso clínico variou de quatro a cinco dias nos três equinos que morreram e de 10 a 15 dias nos dois equinos que recuperaram-se da cólica. À necropsia, os principais achados foram timpanismo intestinal e gástrico e hemorragias na parede intestinal. À microscopia havia enterite linfoplasmocítica e eosinofílica difusa moderada com erosões multifocais e edema submucoso associado à vasculite multifocal. A patogênese da cólica pela ingestão de M. maximus ainda não foi elucidada, no entanto, alguns autores têm sugerido que uma maior concentração de amido presente na forrageira durante o período de chuvas possa ser responsável pela ação tóxica da planta. Contudo as observações aqui levantadas não dão suporte a essa hipótese. Sugere-se como medida profilática evitar o pastejo exclusivo de M. maximus por cavalos, por meio de pastagens alternativas, principalmente durante o início das chuvas e rebrota da pastagem. Demonstra-se que, no Brasil, os surtos de cólica em equinos associados à ingestão de variedades de Megathyrsus, também podem ocorrer fora das regiões Norte e Centro-Oeste, desde que existam condições climáticas especiais.(AU)

Total Stereoselective Michael Addition of N- and S- Nucleophiles to a d-Erythrosyl 1,5-Lactone Derivative. Experimental and Theoretical Studies Devoted to the Synthesis of 2,6-Dideoxy-4-functionalized-d- ribono-hexono-1,4-lactone.

The synthesis of a 1,5-lactone 2,4- O-alkylidene-d-erythrose derivative was found to be a highly stereoselective template in Michael addition trough the reaction of a d-erythrosyl 1,5-lactone derivative with nitrogen and sulfur nucleophiles. The sulfur adducts formed are 1 (d-erythrose derivative):1 (nucleophile), and the nitrogen adducts are 1:2. Both were then treated under HCl to give 2,6-dideoxy-4-functionalized-d- ribono-hexono-1,4-lactone by a reaction cascade in high overall yield. Reaction's scale up even improves the yield. The theoretical and computational results clearly explain the origin of the stereoselectivity, and the energetic course of reactions starting with nitrogen and sulfide nucleophiles. Considering that the 1,4-lactones obtained in this work offer a new molecular scaffold for organic synthesis, these new results provide a solid theoretical platform that can be used to speed up synthesis of other derivatives in a stereo- and regioselective way.